The program is designed to recruit and prepare physician and Ph.D. scientists to become independent research investigators who apply the techniques of recombinant DNA to elucidate fundamental mechanisms of cardiovascular disease. The training is intense and comprehensive, coupled with diverse research experience in physiological and pathological applications ranging from in vitro gene transfer to transgenic and knock-out animals to provide an integrated approach more likely to assure success to the trainee in the 21st century. This program, initiated in 1983, on being awarded the AHA Bugher Foundation Training Grant (1986-92) and subsequently the INRSA (1992-2003), has enrolled a total of 94 trainees. The program consists of three years of training for the M.D. in addition to the clinical fellowship training in cardiology and two years for the PhD. Funding is requested for six positions per year, 5 for M.D. trainees and 1 for the Ph.D. trainee. The third year will be funded by The Methodist Hospital. The success of the program is shown by more than 85% of our graduates remaining in academics and 30 have been selected to participate in national research competitions with 20 winners. The Preceptors have collaborated through training and research for more than a decade, have extensive experience with trainees, all of whom are supported by NIH individual, SCOR, or program project grants located in: Cardiology in the Department of Medicine, and the Departments of Molecular and Human Genetics, Cell Biology, and Pediatrics. Ongoing research themes include: molecular genetics of cardiovascular disorders; genetic defects in coagulation and thrombosis; genetics of lipoprotein disorders; regulation of cardiac growth through growth factors, signal transduction cascades and transcription factors; gene therapy and the use of transgenic mice and homologous recombination to elucidate the pathogenesis of cardiac disease phenotypes. Other major features are: 1) three years protected research time for each trainee; 2) coursework in Bioinformatics, genetics, genetic engineering, biostatistics and grant writing; 3) core facilities of three SCORs and three Program Projects to facilitate technology exchange; and 4) an integrated seminar on molecular genetics of the cardiovascular system. This integrated design has consistently proven to be effective in providing successful independent and competitive investigators in molecular biology of cardiovascular medicine.